The Phase II NIH SBIR grant in ion imaging analysis of biological matrices awarded to Charles Evans and Associates, is producing very promising results. This research uses TOF-SIMS which stigmatically focuses secondary ions produced by bombardment with a Cs+ primary beam. This instrumentation can also produce ion images using a rastered microfocussed primary ion beam, a liquid metal ion gun which produces 69Ga+. SIMS analysis of various biomolecules in tissue-like model matrices using the monatomic primary ion beams is not producing sufficient secondary ions for high quality ion imaging of molecules at the concentrations typically encountered in tissue. In other laboratories increases in secondary ion yields of more than an order of magnitude have been obtained using polyatomic, rather than monatomic, primary ion beams. The first objective of this Phase I research is to adapt the TOF-SIMS mass spectrometer to a polyatomic primary ionbeam source and produce a broad beam of Au cluster ions. With this primary beam, ion imaging could be performed by stigmatically focussing the secondary ions. The second objective is to determine the detection limits and secondary ion yields of selected biomolecules in the tissue-like model matrices and, also in tissue samples, and compare themwith those obtained with monatomic primary ion beams.